Grants and Contracts Details
Abdominal Aortic Aneurysm (AAA) is a progressive focal dilation (infrarenal aortic diameter > 3.0 cm) and weakening of the aorta. It accounts for 11,000 deaths/year in the United States. AAA is associated with extreme rates of death (up to 80%) in the event of aortic rupture. Despite the high morbidity and mortality rate, the mechanism underlying AAA rupture is largely unknown. AAA is characterized by extracellular matrix degradation and loss of vascular smooth muscle cells. These features are associated with infiltration of immune cells in adventitial and medial layers, lead to expansive remodeling of the aortic wall and formation of intraluminal thrombus, which weaken the aortic wall and results in severe complications such as aortic rupture. The goal of this application is to elucidate the role of macrophage pyroptosis in extracellular matrix degradation and the formation of intraluminal thrombus. In the K99 phage, (1) I will capture the occurrence of macrophage pyroptosis in the development of AAA by determining when and where macrophage pyroptosis occur at a molecular level; (2) I will investigate the signaling pathway leads to pyroptosis, specifically whether caspase-1 or 11 is involved. With this information in had, I will then (1) I will investigate the consequences of macrophage pyroptosis on AAA by examining AAA rupture at early and late stage; (2) I will investigate the release of MMPs and tissue factor and analyze elastin degradation and intraluminal clot formation. Together, the studies will elucidate the role of macrophage pyroptosis in AAA and may reveal potential biomarker or therapeutic target.
|Effective start/end date||5/1/19 → 11/30/21|
- National Heart Lung and Blood Institute: $312,962.00
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